Мақаланы E-mail арқылы жіберу Specific Activity of Recombinant Modified Human Glucagon-Like Peptide 1
- Авторлар: Sannikova E.P.1, Bobkova N.V.2, Tatarnikova O.G.2, Yarotskii S.V.1, Askerova E.V.1, Rykalina N.V.1, Yurin V.L.1, Gracheva T.S.1, Klebanov F.A.1, Zalunin I.A.1, Cheperegin S.E.1, Bulushova N.V.1, Kozlov D.G.1
-
Мекемелер:
- State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center, Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
- Institute of Cell Biophysics, Russian Academy of Sciences
- Шығарылым: Том 55, № 7 (2019)
- Беттер: 722-732
- Бөлім: Producers, Biology, Selection, and Gene Engineering
- URL: https://journals.rcsi.science/0003-6838/article/view/153089
- DOI: https://doi.org/10.1134/S0003683819070068
- ID: 153089
Дәйексөз келтіру
Ашық рұқсат
Рұқсат берілді
Тек жазылушылар үшін
Аннотация
An1 original drug, Glypin, has been developed for the treatment of type-II human diabetes mellitus. Its active pharmaceutical substance is a completely biosynthetic, recombinant, modified, human glucagon-like peptide (rmGlp-1) obtained via culturing of E. coli cells. In addition to the GLP-1 portion, which contains the well-known Ala8Gly substitution, the rmGLP-1 protein has an additional amino acid sequence at the C-terminus that includes the heparin-binding peptide of human HB-EGF. Preclinical testing of Glypin specific activity (with Lixumia as a reference drug) was performed. A commercial preparation of Lixumia served as the main reference drug for comparison with the specific activity of Glypin. During preclinical studies of both medicines, it was shown that Glypin and Lixumia have similar mechanisms, power, and time of action upon subcutaneous and intramuscular introductions, as well as comparable therapeutic effects under long-term use. Based on these data, the subcutaneous injection was selected as the main therapeutic method of Glypin administration; the minimal effective dose for Glypin preclinical study was established as 100 μg/kg body mass, and a single dose for human treatment was defined as 0.75 and 1.5 mg. The intranasal introduction of Glypin was observed to have a statistically reliable positive effect on the cognitive capacities of a mouse with Alzheimer’s disease model. The similarity of the characteristics of Glypin and Lixumia shown in our study make it possible to expect that they will have equal therapeutic efficacy with daily use of a single dose.
Авторлар туралы
E. Sannikova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
N. Bobkova
Institute of Cell Biophysics, Russian Academy of Sciences
Email: dg_kozlov@genetika.ru
Ресей, Pushchino, Moscow oblast, 142290
O. Tatarnikova
Institute of Cell Biophysics, Russian Academy of Sciences
Email: dg_kozlov@genetika.ru
Ресей, Pushchino, Moscow oblast, 142290
S. Yarotskii
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
E. Askerova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
N. Rykalina
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
V. Yurin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
T. Gracheva
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
F. Klebanov
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
I. Zalunin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
S. Cheperegin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
N. Bulushova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
D. Kozlov
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Хат алмасуға жауапты Автор.
Email: dg_kozlov@genetika.ru
Ресей, Moscow, 117545
Қосымша файлдар
